Abstract
The mechanism of cell cycle arrest induced by interferon-α (IFN-α) was analysed using a mouse macrophage cell line, BAC1.2F5A. IFN-α added in media before mid-G1 prohibited cells from entering S phase. The blockage of G1/S transition was associated with diminuition of both cyclin D1/cdk4- and cyclin E/cdk2-associated kinase activities. G1 cyclin-associated kinase activities were down-regulated quickly after the addition of IFN-α. Cells treated with IFN-α contained excess amounts of cdk inhibitors which down-regulated G1 cyclin/cdk-associated kinase activities in the proliferating cells and this action was counteracted by exogenously-supplied recombinant cyclin D2/cdk4 complexes. In parallel, accumulation of p19Ink4D and p21Cip1, and their attachment to cdks were up-regulated quickly after the addition of IFN-α. Expression of p19Ink4D and p21Cip1 was potentiated transcriptionally. We concluded that increased attachment of upregulated cdk inhibitors including p19Ink4D and p21Cip1 to G1 cyclin/cdk complexes contributed to diminuition of G1 cyclin/cdk-associated kinase activities and resulting G1 phase arrest during the early phase of treatment with IFN-α.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Matsuoka, M., Tani, K. & Asano, S. Interferon-α-induced G1 phase arrest through up-regulated expression of CDK inhibitors, p19Ink4D and p21Cip1 in mouse macrophages. Oncogene 16, 2075–2086 (1998). https://doi.org/10.1038/sj.onc.1201745
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1201745
Keywords
This article is cited by
-
Essential role of HCMV deubiquitinase in promoting oncogenesis by targeting anti-viral innate immune signaling pathways
Cell Death & Disease (2017)
-
Genomic view of IFN-α response in pre-autoimmune NZB/W and MRL/lpr mice
Genes & Immunity (2007)
-
Interferon-β induces S phase slowing via up-regulated expression of PML in squamous carcinoma cells
Oncogene (2000)